Subproject 3 FM. Fibromyalgia is a prevalent and poorly-treated pain syndrome mediated by unknown mechanisms. The clinical features of fibromyalgia include widespread spontaneous pain and increased sensifivity to pain evoked by blunt pressure Accumulating evidence that includes disfinct subgroups suggests that fibromyalgia is mediated by multiple mechanisms. The common presence of comorbitifies such as disturbed sleep, fatigue, stiffness, and dyscognition in fibromyalgia and the overiap with other disorders such as """"""""episodic migraine, temporomandibular disorders, irritable bowel syndrome and vulvar vestibulitus syndrome suggest that these multiple mechanisms are not specific to a single disorder. One such mechanism is altered descending pain inhibifion. In healthy individuals, noxious stimulation applied anywhere on the body evokes generalized widespread analgesia referred to as Diffuse Noxious Inhibitory Controls (DNIC). Several studies have failed to demonstrate DNIC in patients with fibromyalgia, supporting the parsimonious concept that the widespread pain symptoms in fibromyalgia may result from a defect in this intrinsic widespread analgesic system. Establishing the precise role of DNIC and related regulatory mechanisms in fibromyalgia will greatly advance the scant knowledge about the underiying mechanisms of this disorder and lead to more efficacious, meiDhanistic-based treatments. The proposed work will extensively characterize a large group of fibromyalgia pafients using phenotyping and genotyping methods that will also be applied to related disorders such as vulvar vestibulitus syndrome and episodic migraine. The central hypothesis for the proposed research is that fibromyalgia represents the combined effects of mulfiple mechanisms that interfere with tonic pain inhibition, resulfing in the spontaneous and evoked pain symptomatology observed with fibromyalgia. This hypothesis will be investigated by additional methods that examine causal relationships between the function of pain inhibitory systems and the magnitude of clinical pain, and that use functional neuroimaging to evaluate the role of pain inhibitory mechanisms. Identifying multiple common mechanisms will provide targets for future therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS045685-10
Application #
8650340
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
10
Fiscal Year
2014
Total Cost
$109,941
Indirect Cost
$33,562
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Ciszek, Brittney P; O'Buckley, Sandra C; Nackley, Andrea G (2016) Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors. Anesthesiology 124:1122-35
Moss, Chailee F; Damitz, Lynn A; Gracely, Richard H et al. (2016) Dorsal clitoral nerve injury following transobturator midurethral sling. J Pain Res 9:727-730
Oladosu, Folabomi A; Ciszek, Brittney P; O'Buckley, Sandra C et al. (2016) Novel intrathecal and subcutaneous catheter delivery systems in the mouse. J Neurosci Methods 264:119-28
Wu, Cindy; Damitz, Lynn; Karrat, Kimberly M et al. (2016) Clitoral Epidermal Inclusion Cyst Resection With Intraoperative Sensory Nerve Mapping Technique. Female Pelvic Med Reconstr Surg 22:e24-6
Ciszek, Brittney P; Khan, Asma A; Dang, Hong et al. (2015) MicroRNA expression profiles differentiate chronic pain condition subtypes. Transl Res 166:706-720.e11
Oladosu, Folabomi A; Conrad, Matthew S; O'Buckley, Sandra C et al. (2015) Mu Opioid Splice Variant MOR-1K Contributes to the Development of Opioid-Induced Hyperalgesia. PLoS One 10:e0135711
Convertino, Marino; Samoshkin, Alexander; Gauthier, Josee et al. (2015) μ-Opioid receptor 6-transmembrane isoform: A potential therapeutic target for new effective opioids. Prog Neuropsychopharmacol Biol Psychiatry 62:61-7
Applebaum, Elizabeth; Nackley, Andrea G; Bair, Eric et al. (2015) Genetic Variants in Cyclooxygenase-2 Contribute to Post-treatment Pain among Endodontic Patients. J Endod 41:1214-8
Oladosu, Folabomi A; Maixner, William; Nackley, Andrea G (2015) Alternative Splicing of G Protein-Coupled Receptors: Relevance to Pain Management. Mayo Clin Proc 90:1135-51
Meloto, Carolina B; Segall, Samantha K; Smith, Shad et al. (2015) COMT gene locus: new functional variants. Pain 156:2072-83

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